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1. Introduction
The survival rate of the childhood cancer patients has significantly improved because of the progress in treatment methods. However, the intensification of therapy at young age causes many long-term complications. One of the serious problems in pediatric oncology is a several-fold increase of secondary cancer risk, in comparison to the general population [1–3]. The most common childhood malignancy is acute lymphoblastic leukemia (ALL), followed by solid tumors such as brain neoplasms, neuroblastoma, nephroblastoma, and rhabdomyosarcoma. Conversely, the secondary malignancies in children are represented mainly by acute nonlymphoblastic leukemias, brain tumors, and thyroid cancer. Multiple factors may increase the risk of developing these secondary malignancies in childhood cancer survivors with both intrinsic and environmental aspects [2–4]. They are probably caused by the fact that ionizing radiation, multimodal chemotherapy, and immunosuppression interfere with the ongoing developmental and maturation processes. Some children can develop metachronic neoplasms either due to genetic syndromes such as neurofibromatosis, Li-Fraumeni, and Beckwith-Wiedemann syndromes or through unsettled, most probably genetic, susceptibility [1–3, 5].
The relation between the child’s age, tumor histology, and the latent period for the secondary neoplasm development has been confirmed [1, 5]. Radiation therapy of the CNS region is associated with an increased risk of any subsequent brain tumor, especially gliomas (secondary malignant glioma, SMG) [4, 6, 7]. Primary pediatric brain tumors show age and site dependency, arising from topographically discrete progenitor cells. High grade pediatric gliomas are rather infrequent in general population; they comprise histological categories such as glioblastoma, anaplastic astrocytomas, anaplastic oligodendrogliomas, and diffuse intrinsic pontine glioma. Their gene expression and DNA methylation signatures are distinctive, often reflecting a developmental context [8–10]. SMGs arise as a late side effect of ALL or primary brain tumors treatment, usually developing within the irradiation field in subsequent 10 years. ALL patients typically receive chemotherapy and craniospinal radiotherapy and achieve up to 90% cure rate, but with a significant risk of a secondary cancer [11, 12]. The clinical presentation of SMG is not specific, and also radiologically it can be suggestive of a primary cancer recurrence, metastasis, inflammatory lesion, or radionecrosis....